7180
J. Org. Chem. 1993,58, 7180-7184
Stereoselective Synthesis of 2,B-Dihydrofurans by Sequential SNZ’ Cleavage of Alkynyloxiranes and Ag+-CatalyzedCyclization of the Allenylcarbinol Products James A. Marshall’ and Kevin G. Pinney
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208 Received August 17, 1993.
The alkynyloxiranes 5a,b, 7, and 18 afford mainly the anti SN2’ products 6a,b, 8, and 19a upon treatment with MezCuLi. The derived primary alcohol silyl ethers 9a,b, 10, and 19b-d undergo Ag+-catalyzed cyclization to the 2,Bdihydrofurans lla,b, 12, and 20b-d. Diol 26 affords mainly the fused ring 2,Bdihydrofuran 32 under these conditions. The stereochemistry of dihydrofuran 20a was confirmed by conversion to the known epoxide 21a. 2,B-Disubstituted tetrahydrofurans are important structural elements of polyether antibiotics’ and various polyene mycotoxins.2 An interest in developing general stereocontrolled routes to such compounds prompted our examination of the sequence depicted in eq 1.
Me
R’
I
xR2+ -0TBS
(Ph3P)zPdCl~ Mef
OTBS
R’
cut
l a R’ = CH~OH,R‘ = H 1b R’ = H, R2 = CHZOH
2a (89%) 2b (82%)
(3)
I
II
111
3a (98%)
It is well established that allenylcarbinols (11) cyclize to 2,bdihydrofurans (111) with high stereoselectivity.3 However, the SN2’ displacement of alkynyloxiranes (I) can lead to anti or syn products, depending on the copper reagent and, to some extent, the s ~ b s t i t u e n t s .In ~ our studies on sN2’ displacements of vinyloxiranes by cuprates, we found that an allylic hydroxy grouping greatly assists the anti reaction pathway (eq 2).5 It was of interest to examine the possibility of such a directing effect for alkynyloxiranes I (R4= CH20H) as well.
IV
4a R’ 4b R’ Sa R‘ 5b R’
= CHzOMOM, R‘ = H, R3 = TBS = H, R‘ = CHZOMOM, R3 = TBS = CHzOMOM, R2 = R3 = H = R3 = H, R2 = CHZOMOM
epoxy alcohols 3a and 3b with MOMC1, andi-PrzNEt (HB) afforded the ethers 4a and 4b. Desilylation with TBAF gave the alcohols of interest, 5a and 5b. A third alkynyloxirane system, 7, was prepared from alcohol 3a by benzylation (BnBr, NaH) and subsequent TBS cleavage. Each of the foregoing alcohols 5a, 7, and 5b afforded the SN2’ products, 6a, 8, and 6b, in high yield as 9O:lO or better mixtures of diastereoisomers upon treatment with the Gilman methyl cuprate (eqs 4 and 51.8 In addition,
V
Suitable prototype systems were prepared by Sonogashiro couplings of vinylic iodides la and lb7 with the TBS ether of propargyl alcohol (eq 3). Epoxidation of the double bond with m-CPBA followed by protection of the Abstract published in Aduance ACS Abstracts, November 1,1993. (1) Boivin, T. L. B. Tetrahedron 1987,43, 3309. (2) Ganguli, M.; Burka, L. T.; Harris, T. M. J. Org. Chem. 1984,49, 3762. Sakabe, N.; Goto, T.; Hirata, Y. Tetrahedron 1977, 33, 3077. Syntheses: Whang, K.; Cooke, R. J.; Okay, G.; Cha, J. K. J. Am. Chem. SOC.1990,112,8985. Hatakeyama, 5.;Sakurai, K.; Numata, H.; Ochi, N.; Takano, S. J. Am. Chem. Soc. 1988,110,5201. (3) Olseon, L.;Claesson, A. Synthesis 1979,743. Marshall, J. A.; Wang, X.-j.J. Org. Chem. 1991, 56, 4913. (4) Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J. F. Tetrahedron 1991, 47, 1677. Oehlschlager, A. C.; Czyzewska, E. Tetrahedron Lett. 1983,24, 5587. (5) Marshall, J. A. Chem. Rev. 1989,89,1503. Marshall, J. A.; Blough, B. E. J. Org. Chem. 1991,56, 2225. (6) Sonogaehiro,K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
--”..
Ada7
(7) (a) Lautens, M.; Hubom, A. H. Tetrahedron Lett. 1990,31,3105. (b)Cochrane, J. S.; Hanson, J. R. J. Chem. SOC.,Perkin Tram. 1 1972, 3, 361.
0022-3263/93/1958-7180$04.00/0
MezCuLi
RO/;
Me L * - M e OH
JOH (4)
OR 5a R=MOM 7 R=Bn
6a R = MOM (75%, >90:10) 8 R = Bn (91%, 98:2)
OMOM 5b R = H 4b R = TBS
6b R I H (71%, 93:7) 9b R = TBS (SO%, 80:20)
up to 15% of protonolysis products (H instead of Me a t carbon-5 (compounds 6a, 6b, 9b) or carbon-2 (compounds 8, 19a)) were also formed. 0 1993 American Chemical Society
J. Org. Chem., Vol. 58, No. 25, 1993 7181
Stereoselective Synthesis of 2,5-Dihydrofurans The TBS ether 4b gave rise to an 8020 mixture of diastereomers under these conditions. Thus, the hydroxy substituent clearly improves the diastereoselectivity of the displacement, in keeping with our previous findings.s We also examined other cuprates, MeCu(CN)Li, MezCu(CN)Liz, and MeMgBrCuBr-SMez? with epoxide 5b. All gave substantially lower yields (30%,30%,10%1. In the latter case, 50 % of the sN2 product was produced. In view of the high diastereoselectivity of these reactions and literature analogy4 we assumed that the major products were formed by the anti pathway. This assumption was later confirmed. Selective silylation of the SN2' products 6a,b and 8 followed by treatment of the derived secondary alcohols 9a,b, and 10 with AgN03 in aqueous acetone afforded the 2,5-dihydrofurans 1 la,b and 12 in high yield (eq 6). When
9a R' = CH20MOM,R2 = H 9b R' = H, R2 = CH$OMOM 10 R' = CH20Bn, R = H
l l a (86%) 11b (78%) 12 (91%)
a mixture of diastereomeric alcohols was used, an identical mixture of dihydrofuran diastereomers was formed in keeping with a highly stereoselective or stereospecific process. The methyl-substituted alkynyloxirane 18 was prepared from enyne 131° by selective deprotection to alcohol 14 and hydrogenolysis of the derived chloride 15 and then epoxidation with m-CPBA and removal of the DPS grouping (eq 7). Cuprate addition proceeded as before to
MeAH 13 R = CHzOTBS 15 R=CH2CI 16 R=CH3
M ~ CL I ,icl
l7 R == HD P 3 T B A F 18 R
L-Selectride (81%)
(7)
19a l9b 19c 19d
R = H (70%, 98:2) R =TBS
R=DPS R=TIPS
20a 20b 20c 206
R=H
R = TBS (81%) R = DPS (82%) R = TIPS (90%)
yield allenediol 19a along with the corresponding protonolysis product. Addition of CH3I to the cuprate reaction effectivelysuppressed formation of this byproduct ( 9O:lO) and the protonolysis product as a clear liquid 1H-NMR (CDCls) 6 4.63 and 4.60 (AB,, Jm = 6.6 Hz),4.10 (m), 3.93 (m), 3.62 (dd, J = 10.4, 3.7 Hz), 3.56 (dd, J = 10.4, 5.3 Hz), 3.32 (a), 2.90 (m), 1.70 (s), 1.66 (8); "C-NMR (CDCls, 75 MHz) 6 195.3, 104.2, 103.9, 96.8, 71.4, 70.1, 63.4, 55.4, 15.9, 15.6. mJ-(ZR,4S)- 1-(Methoxymethoxy)-3,S-di~thyl-3,4-hexadiene-2,6-diol(6b). The procedure described for 6a was employed with epoxide 5b (0.150 g, 0.806 mmol). Purification by flash chromatography (EtOAc)afforded 0.1113 g (0.574 mmol, 71%) of a 90:lOmixtureof allene 6b (antixyn > 93:7) and the protonolysis product as a clear liquid lH-NMR (CDCl3) 6 4.65 (s), 4.18 (m),
J. Org. Chem., Vol. 58, No. 25,1993 7183 4.00 (m), 3.66 (dd, J = 10.4,4.1 Hz), 3.54 (dd, J = 10.4,6.5 Hz), 3.37 (a), 2.85 (d, J = 5.2 Hz), 2.46 (t, J = 5.3 Hz), 1.74 (e), 1.67 ( 8 ) ; MS (CI) (M H)+ 203; (M + N&)+ 220; HRMS (EI) M OCHs calcd for C~HISOS 171.1021, found 171.1017. Anal. Calcd for Cl0Hl804 C, 59.39; H, 8.97. Found C, 59.19; H, 9.01. rel-(2S,4S)-6-[ ( tert-Butyldimethylsilyl)oxy]-1-(methoxymethoxy)-3,5-dimethy1-3,4-hesadien-2-01(9a). To a wellstirred solution of diol 6a (0.070 g, 0.346 mmol, antksyn > 90:lO) in CH&& (7 mL) waa added EbN (0.046 g, 0.450 mmol), D W (0.002 g, 0.017 mmol), and TBSCl(O.078 g, 0.519 "01). After 19 h, additional EhN (0.046 g, 0.450 mmol) and TBSCl (0.030 g, 0.199 "01) were added. After 5 h, water was added, and the product was isolated by extraction with CH2C12. Purification by flash chromatography (50:50 EtOAc/hexane) afforded ether 9a (0.099 g, 0.313 mmol, 90%, antksyn > 90.10) as a clear liquid lH-NMR (CDCh) 6 4.67 and 4.64 (AB,, JAB= 6.6 Hz), 4.16 (m), 4.05 (a), 3.68 (dd, J = 10.5, 3.1 Hz), 3.47 (dd, J = 10.5.7.8 Hz), 3.37 (s),2.42 (d, J = 4.6 Hz), 1.72 (a ), 1.68 (a), 0.88 (s),0.042 (8); IR (film) u 3455 (br), 1970,1464 cm-l. &(2&4S)-6-[ (tert-Butyldimethyleilyl)oxy]-1-(methoxymethoxy)-3,5-dimethyl-3,4-hexadien-2-01(9b). To a wellstirred solution of diol 6b (0.108 g, 0.534 mmol, antksyn > 937) in CH2Cl2 (8 mL) was added imidazole (0.044 g, 0.641 mmol) followed by TBSCl(O.105 g, 0.694 mmol). After 2 h, water was added, and the product was isolated by extraction with CH2C12. Purification by flash chromatography (50:50 EtOAc/hexane) afforded ether 9b (0.149 g, 0.471 mmol, 88%,antksyn > 93:7) as a clear liquid: lH-NMR (CDCls) 6 4.65 (e), 4.15 (m), 4.04 (d, J =1.7Hz),3.65(dd,J=10.4,3.2Hz),3.47(dd,J=10.4,7.6Hz), 3.36 (s), 2.46 (d, J = 4.1 Hz), 1.71 (s), 1.67 (a), 0.865 (s), 0.0324 ( 8 ) ; MS (CI) (M + H)+ 317; (M + N&)+ 334; HRMS (EI) M CHScalcd for C&aO4Si 301.1835, found 301.1824. Anal. Calcd for C&20fik C, 60.72; H, 10.19. Found: C, 60.56; H, 10.14. rel-(25,69)-2,4-Dimethyl-2-[ [(tert-butyldimethylsily1)oxylmethyll-C[(methoxymethoxy)methyl]-2,S-dihydrofuran (1la). To a well-stirred solution of allene 9a (0.042 g, 0.133 mmol, anti:syn > 90:lO) in 1.5mL of acetone and 1.0 mL of H20 was added AgNOs (0.018 g, 0.106 mmol) and CaCOs (0.011 g, 0.106 mmol) in the dark. After 20 h, water was added, and the product was isolated by extraction with EtOAc. Purification by flash chromatography (silicagel, 5050 EtOAc/hexane) afforded dihydrofuran lla (0.036 g, 0.114 mmol,86%, &:tram > 90:lO) as a clear, colorless liquid: 'H-NMR (CDCL) 6 5.45 (t, J = 1.7 Hz), 4.75 (m), 4.64 and 4.62 (ABq, Jm = 6.5 Hz), 3.63 (dd, J = 10.4, 3.2 Hz), 3.50 (dd, J = 10.4, 6.1 Hz), 3.48 (m ), 3.34 (e), 1.69 (t,J = 1.2 Hz), 1.22 (e), 0.855 (s), 0.0005 (8); "C-NMR (CDCL, 75MHz)G 135.2,128.5,96.7,89.9,86.4,70.2,69.9,55.2,25.9,23.2, 18.3, 12.6, -5.39, -5.43; IR (film) u 1671 cm-1. re1-(29,6R)-2,4-Dimethyl-2-[ [(tert-butyldimethyleily1)oxy]methyl 1-5-[(methoxymet hoxy )met hyl]-2,5-dihydrof uran (11b). The procedure described for 1la was employedwith allene9b (0.125g,0.395mmol,anti:syn> 937; 12h). Purification by flashchromatography(silicagel, 2&8OEtOAc/hexane)afforded dihydrofuran l l b (0.097 g, 0.306 mmol,78%, tram:& = 93:7 by GC) as a clear, colorless liquid 'H-NMR (CDClS)6 5.44 (t,J = 1.7 Hz), 4.72 (m), 4.66 and 4.64 (ABq, Jm = 9.1 Hz), 3.67 (dd, J = 10.7, 3.1 Hz), 3.52 (dd, J = 10.7, 5.2 Hz), 3.48 (m), 3.35 (s), 1.71 (t, J = 1.2 Hz), 1.23 (s), 0.851 (a), 0.0005 (8); MS (CI) (M H)+ 317; (M + NH4)+334; HRMS (E11 M - OCHs calcd for ClSHaOsSi285.1886, found 285.1887. Anal. Calcd for Cl~H9204Si: C, 60.72; H, 10.19. Found C, 60.56; H, 10.20. re1-(3S,bR)-2,4-Dimethy1-2,3-hexadiene1,5-diol( 19a). To a well-stirred solution of CUI (2.29%12.0 mmol) in THF (40 mL) at -25 OC was added CH&i (17.2 mL of a 1.4 M solution in EtO). After 30 min, alkynyloxirane 18 (0.760 g, 6.02 mmol) in THF (2.0 mL) was added in one portion. After 10 s, CHJ (3.42 g, 24.1 mmol) was added followed immediately by quenching with 1:l 3 % NH4OH/saturated NHdCl(20 mL, dropwise, exothermic!). The solutionwas layered with EkO (20mL) and vigorously stirred for 1 h. The product was isolated by extraction with EtO. Purification by flaah chromatography (silicagel, EhO)afforded 0.602 g (4.23 mmol, 70%)of a 93:7 mixture of diol 19a ( a n t h y n > 982) and the protonolysis product as a clear, colorless liquid: 'H-NMR (CDCla) 6 4.16 (q, J = 6.4 Hz), 3.95 and 3.90 (AB,,Jm = 13.0 Hz), 3.27 (be), 1.64 (a), 1.63 (s), 1.23 (d, J 6.4 Hz): "CNMR (CDCls)b 195.6,106.3,101.8,69.0,63.8,21.4,15.9,14.3; MS
+
+
7184
J. Org. Chem., Vol. 58, No. 25, 1993
(CI) (M + NH4)+160; HRMS (E11 M - H2O calcd for CSHIZO 124.0888,found 124.0887. re&(3S,bR)- 1-[ (tert-Butyldimethylsilyl)oxy]-2,4-dimethyl-2,3-he.adien-S-o1(19b). The procedure described for 9awas followed with diol 198 (0.491 g, 2.95 mmol, anti:syn > 98:2; 15 h). Purification by flash chromatography (silicagel, 2080EGO/ hexane) afforded ether 19b (0.650g, 2.53mmol, 86%) as a clear, colorless liquid 'H-NMR (CDCl3) 6 4.14 (q, J = 6.4 Hz), 4.05 (a), 1.684 (a), 1.683 (E), 1.25 (d, J = 6.4 Hz), 0.878 (s), 0.045 ( 8 ) ; '3CNMR (CDCh, 125 MHz) 6 196.1, 105.4,103.1,69.2,65.6, 26.2, 22.4,18.7,16.2,15.4,-4.88,-4.93;MS (CI) (M + H)+,257;(M + NH4)+274; HRMS (EI) M - H calcd for ClrHnOzSi 255.1780, found 255.1779. Anal. Calcd for C14H~02Si:C, 65.57;H, 11.01. Found C, 65.72;H, 11.07. rel-(2R,bR)-2-[[ (tert-Butyldimethylsilyl)oxy]methyl]2,4,S-trimethyl-2,S-dihydrofuran(20b). The procedure described for l la was followedwith allene 19b (0.217g, 0.846 mmol, anti:syn > 982). Purification by flash chromatography (silica gel, 2080 EhO/hexane) gave dihydrofuran 20b (0.176g, 0.686 mmol, 81 % ) as a clear, colorlessliquid 'H-NMR (CDCls)S 5.33 (t,J 1.6 He), 4.71 (9,J = 6.4 Hz), 3.46 and 3.41 (AB,,JAB= 9.7 Hz), 1.64 (t,J = 1.3 Hz), 1.22 (d, J = 6.4 Hz), 1.20 (a), 0.868 (a), 0.0171 (e); '3C-NMR (CDC13) 6 139.7,126.5,89.5,83.6,71.2, 26.3,23.6,21.6,18.7,12.6, -4.97,-5.02;MS (CI) (M + H)+,257; (M+ Nf4)+274;HRMS (EI) M-Hcalcdfor Cl,HnOfii255.1780, found 255.1782. Anal. Calcd for C14HaOzSi: C, 65.57;H, 11.01. Found C, 65.65; H, 10.97. rel-(2R,bR)-2-(Hydroxymethyl)-2,4,S-trimet hyl-2,s-dihydrofuran (208). To a solution of ether 20b (0.645g, 2.51mmol) was added TBAF (7.5mL of a 1.0 M solution in THF). After 2 h, water was added, and the product was isolated byextraction (EhO,HzO, brine, MgS0,). Solventwas removedtoafford alcohol 20a" (0.357g, 2.51 mmol, 100%) as a clear, colorless liquid. A small quantity was purified by flash chromatography (silicagel, 1:l EhO/hexane) for characterization: lH-NMR (CDCh, 300 MHz) S 5.25 (t,J = 1.7 Hz), 4.74 (qq, J = 2.0,6.4 Hz), 3.45 and 3.41 (AB,, Jm 11.4 Hz), 1.80 (be), 1.67 (dd, J = 1.5,1.1 Hz), 1.26 (d, J = 6.4Hz), 1.19( 8 ) : '3C-NMR (CDCl3,75MHz) 6 141.0, 125.1,89.4,82.9,68.3,22.8,21.0,12.3 [lit." 1H-NMR (CDCl3,gO MHz) 6 5.3 (br a), 4.77 (q, J = 7.0 Hz), 3.49 (a), 2.48 (br s), 1.7 (d, J = 1 Hz), 1.29 (d, J = 7 Hz), 1.2 (a)]. rel-(2S,3R,4S,bR)-Z-[[(Triisopropylsilyl)oxy]methyl]-3,4epoxy-2,4,S-trimethyl-2,3,4,S-tetrahydrofuran(22d). The procedure described for 3a was employedwith dihydrofuran 20d (0.158g,0.529 mmol, 15 h). The product isolated by extraction with CHzClz was a 35:65 mixture of epoxides 21d and 22d (0.157 g, 0.499 mmol, 94%), purified by flash chromatography (silica gel, 2080 EhO/hexane): 21d 'H-NMR (CDCh) 6 4.13 (9, J = 6.8 Hz), 3.61 and 3.60 (AB,, JAB 9.9 Hz), 3.55 (s), 1.42 (s), 1.25 (s), 1.20 (d, J = 6.8 Hz),1.05 (m);1%-NMR (CDCls,125 MHz) 682.3,77.7,69.4,68.3, 68.0,20.5,18.9,18.37,18.36,14.4,12.3;MS (CI) (M + H)+ 316, (M + NH4)+332; HRMS (EI) M - i-Pr calcd for ClrHnO3Si
Marshall and Pinney 271.1729,found 271.1726. Anal. Calcd for C1,HaO&i: C, 64.92; H, 10.90. Found C, 65.03;H, 10.97. 22d 'H-NMR (CDCL) 6 3.85 (9, J 6.2 Hz), 3.75 and 3.46 (AB,,JAB= 8.8 Hz), 3.37 (s), 1.42 (E), 1.20 (E), 1.16 (d, J = 6.2 Hz), 1.04 (m); I3C-NMR(CDCL,75 MHz) d 80.3,73.8,66.2,65.8, 65.5,18.6,18.0,17.9,14.0,13.8,11.9; MS (CI) (M + H)+315,(M + NH4)+332;HRMS (EI) M- i-Pr calcd for ClrH~03Si271.1729, found 271.1732. Anal. Calcd for C17HaO3Si: C, 64.92;H, 10.90. Found C, 64.89; H, 10.98. re1-(25,3S,4R,bR)-2-(Hydroxymethyl)-3,4-epoxy-2,4$trimethyl-2,3,4,S-tetrahydrofuran(218). To a well stirred solution of silyl ether 21c (0.073g, 0.184mmol) in CHZClz (1.0mL) was added TBAF (0.096g, 0.368 "01). After 20 h, water was added, and the product was isolated by extraction (CHZC12,HzO, brine, MgSO4). Purification by flash chromatography (silicagel, 5050 EtOAc/hexane) afforded alcohol 2la (0.024g, 0.152 mmol, 82%) as a clear, colorless liquid lH-NMR (CDCg, 500 MHz) 8 4.17 (q, J = 6.8Hz), 3.53 (bs), 3.40 (a), 1.80 (bs), 1.44 (a), 1.25 (a), 1.22 (d, J = 6.8Hz); 'H-NMR (C& 500 MHz) 6 4.10(q, J = 6.8 Hz), 3.23 and 3.17 (AB,,JAB= 10.8 Hz), 3.02 (E), 1.31 (E), 1.03 (a), 0.877 (d, J = 6.8Hz) [lit.'z 'H-NMR (CDCla, 400 MHz) d 4.19 (q, J = 6.8 Hz), 3.49 (a), 3.43 (a), 1.46 (a), 1.27 (a), 1.25 (d, J = 6.8 Hz)]; MS (CI) (M + H)+ 159,(M + NH4)+ 176;HRMS (CI) M + H calcd for CJ-€laO3159.1021,found, 159.1024. ml-(ZS,3&4S,bR)-2-( Hydroxymethyl)-3,4-epoxy-2,4,S-trimethyl-2,3,4,5-tetrahydrofuran (228). The procedure described for 2la was employed with silyl ether 22c (O.O96g, 0.242 mmol, 12 h). Purification by flash chromatography (silica gel, EhO) afforded alcohol 228 (0.030g, 0.190mmol, 78%) as a clear, colorless liquid 'H-NMR (CDCl3)6 3.87 (q, J = 6.2Hz), 3.68and 3.61 (AB,, JAB= 11.1 Hz), 3.32 (e), 2.26 (be), 1.42 (a), 1.19 (d,J = 6.2 Hz), 1.13 ( 8 ) ; 'H-NMR (C&) 6 3.70 and 3.62 (AB,,Jm 10.6 Hz), 3.52 (q, J = 6.2Hz), 2.91 (a), 2.01 (bs), 1.11 (d, J = 6.2 Hz), 0.986 (a), 0.953 (a); MS (CI) (M + H)+ 159,(M + N*)+ 176; HRMS (CI) M + H calcd for C8HlsOa 159.1021,found, 159.1015. Anal. Calcd for C&&: C, 60.74; H, 8.92. Found 60.49; H, 8.87.
Acknowledgment. Support for this work was provided by Research Grant CHE 8912475 from the National Science Foundation. K.G.P. thanks the NIH for a postdoctoral fellowship (5-F32-CA0893402)from the National Cancer Institute. We are indebted to Professor Jin Cha for providing comparison spectra and for helpful discussions. Supplementary Material Available: Experimental procedures for compounds 7-8, 10, 12-18, 19c-d, 20c-0, 2122(a,b,c,e), and 23-32 and selected 'H and 13C NMR spectra (46 pages). This material is contained in libraries on microfiche, immediately follows this article in the microfilm version of the journal, and can be ordered from the ACS; see any current masthead page for ordering information.
